Journal: bioRxiv

Article Title: Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction

doi: 10.64898/2026.01.27.701787

Figure Lengend Snippet: A. Immunoblot of synaptosome isolation fractions (s, supernatant; cp, cell pellet; cyt, cytosolic; syn, synaptosomes) from mouse primary cortical neurons incubated with (+ filaments) and without (- filaments) FTLD-TDP Type A patient brain-derived TDP-43 filaments for 3 d, probed with antibodies against postsynaptic density protein 95 (PSD95, top), pS409/410 TDP-43 (pTDP-43, middle) and TDP-43 (bottom). The arrows indicate full-length (FL) TDP-43 and C-terminal fragments (CTFs) of TDP-43. B. Denoised tomographic slices of synaptosomes from mouse primary cortical neurons incubated with FTLD-TDP Type A patient brain-derived TDP-43 filaments for 3 d. TDP-43 filaments (magenta arrows), example synaptic vesicles (cyan arrows) and the postsynaptic density (yellow arrow) are indicated. C and D. Denoised tomographic slices showing TDP-43 filaments (magenta arrows). making contacts (green arrows) with synaptic vesicles (cyan arrows) (C) and the presynaptic plasma membrane (yellow arrows) (D) . B-D. Scale bars, 50 nm.

Article Snippet: The following the primary antibodies were used: anti-phospho-serine 409 and 410 TDP-43 (Cosmo-Bio, TIPPTD-M01; 1:3000); anti-TDP-43 (Proteintech, 10782-2-AP; 1:5000); and anti-postsynaptic density protein 95 (NeuroMab, 75-028; 1:1000).

Techniques: Western Blot, Isolation, Incubation, Derivative Assay, Clinical Proteomics, Membrane